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Genome-wide association study reveals two new risk loci for bipolar disorder

Author

Listed:
  • Thomas W. Mühleisen

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn
    Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich)

  • Markus Leber

    (Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn
    German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany)

  • Thomas G. Schulze

    (University of Go¨ttingen)

  • Jana Strohmaier

    (Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University)

  • Franziska Degenhardt

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Jens Treutlein

    (Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University)

  • Manuel Mattheisen

    (Aarhus University
    Institute for Genomic Mathematics, University of Bonn)

  • Andreas J. Forstner

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Johannes Schumacher

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • René Breuer

    (Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University)

  • Sandra Meier

    (Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University)

  • Stefan Herms

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn
    University of Basel)

  • Per Hoffmann

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn
    Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich
    University of Basel)

  • André Lacour

    (German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany)

  • Stephanie H. Witt

    (Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University)

  • Andreas Reif

    (Psychosomatics and Psychotherapy, University of Würzburg)

  • Bertram Müller-Myhsok

    (Statistical Genetics, Max Planck Institute of Psychiatry
    Munich Cluster for Systems Neurology (SyNergy)
    Institute of Translational Medicine, University of Liverpool)

  • Susanne Lucae

    (Statistical Genetics, Max Planck Institute of Psychiatry)

  • Wolfgang Maier

    (University of Bonn)

  • Markus Schwarz

    (Psychiatric Center Nordbaden)

  • Helmut Vedder

    (Psychiatric Center Nordbaden)

  • Jutta Kammerer-Ciernioch

    (Psychiatric Center Nordbaden)

  • Andrea Pfennig

    (University Hospital)

  • Michael Bauer

    (University Hospital)

  • Martin Hautzinger

    (Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen)

  • Susanne Moebus

    (Institute of Medical Informatics, Biometry, and Epidemiology, University Duisburg-Essen)

  • Lutz Priebe

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Piotr M. Czerski

    (Poznan University of Medical Sciences)

  • Joanna Hauser

    (Poznan University of Medical Sciences)

  • Jolanta Lissowska

    (Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology)

  • Neonila Szeszenia-Dabrowska

    (Nofer Institute of Occupational Medicine)

  • Paul Brennan

    (Genetic Epidemiology Group, International Agency for Research on Cancer (IARC))

  • James D. McKay

    (Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC))

  • Adam Wright

    (School of Psychiatry, University of New South Wales
    Black Dog Institute, Prince of Wales Hospital)

  • Philip B. Mitchell

    (School of Psychiatry, University of New South Wales
    Black Dog Institute, Prince of Wales Hospital)

  • Janice M. Fullerton

    (Neuroscience Research Australia
    School of Medical Sciences, Faculty of Medicine, University of New South Wales)

  • Peter R. Schofield

    (Neuroscience Research Australia
    School of Medical Sciences, Faculty of Medicine, University of New South Wales)

  • Grant W. Montgomery

    (Queensland Institute of Medical Research (QIMR))

  • Sarah E. Medland

    (Queensland Institute of Medical Research (QIMR))

  • Scott D. Gordon

    (Queensland Institute of Medical Research (QIMR))

  • Nicholas G. Martin

    (Queensland Institute of Medical Research (QIMR))

  • Valery Krasnow

    (Moscow Research Institute of Psychiatry)

  • Alexander Chuchalin

    (Institute of Pulmonology, Russian State Medical University)

  • Gulja Babadjanova

    (Institute of Pulmonology, Russian State Medical University)

  • Galina Pantelejeva

    (Russian Academy of Medical Sciences, Mental Health Research Center)

  • Lilia I. Abramova

    (Russian Academy of Medical Sciences, Mental Health Research Center)

  • Alexander S. Tiganov

    (Russian Academy of Medical Sciences, Mental Health Research Center)

  • Alexey Polonikov

    (Medical Genetics and Ecology, Kursk State Medical University)

  • Elza Khusnutdinova

    (Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences)

  • Martin Alda

    (Dalhousie University
    The International Group for the Study of Lithium-Treated Patients (IGSLI))

  • Paul Grof

    (The International Group for the Study of Lithium-Treated Patients (IGSLI)
    Mood Disorders Center of Ottawa
    University of Toronto)

  • Guy A. Rouleau

    (Montreal Neurological Hospital and Institute, McGill University)

  • Gustavo Turecki

    (Douglas Hospital Research Institute, McGill University)

  • Catherine Laprise

    (Université du Québec à Chicoutimi (UQAC))

  • Fabio Rivas

    (Hospital Regional Universitario Carlos Haya)

  • Fermin Mayoral

    (Hospital Regional Universitario Carlos Haya)

  • Manolis Kogevinas

    (Center for Research in Environmental Epidemiology (CREAL))

  • Maria Grigoroiu-Serbanescu

    (Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital)

  • Peter Propping

    (Institute of Human Genetics, University of Bonn)

  • Tim Becker

    (Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn
    German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany)

  • Marcella Rietschel

    (Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University)

  • Markus M. Nöthen

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn)

  • Sven Cichon

    (Institute of Human Genetics, University of Bonn
    Life & Brain Center, University of Bonn
    Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich
    University of Basel)

Abstract

Bipolar disorder (BD) is a common and highly heritable mental illness and genome-wide association studies (GWAS) have robustly identified the first common genetic variants involved in disease aetiology. The data also provide strong evidence for the presence of multiple additional risk loci, each contributing a relatively small effect to BD susceptibility. Large samples are necessary to detect these risk loci. Here we present results from the largest BD GWAS to date by investigating 2.3 million single-nucleotide polymorphisms (SNPs) in a sample of 24,025 patients and controls. We detect 56 genome-wide significant SNPs in five chromosomal regions including previously reported risk loci ANK3, ODZ4 and TRANK1, as well as the risk locus ADCY2 (5p15.31) and a region between MIR2113 and POU3F2 (6q16.1). ADCY2 is a key enzyme in cAMP signalling and our finding provides new insights into the biological mechanisms involved in the development of BD.

Suggested Citation

  • Thomas W. Mühleisen & Markus Leber & Thomas G. Schulze & Jana Strohmaier & Franziska Degenhardt & Jens Treutlein & Manuel Mattheisen & Andreas J. Forstner & Johannes Schumacher & René Breuer & Sandra , 2014. "Genome-wide association study reveals two new risk loci for bipolar disorder," Nature Communications, Nature, vol. 5(1), pages 1-8, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4339
    DOI: 10.1038/ncomms4339
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